Indacaterol/glycopyrronium reduces the risk of clinically important deterioration after direct switch from baseline therapies in patients with moderate COPD: a post hoc analysis of the CRYSTAL study

Figures & data

Figure 1 Study design of the groups that switched to IND/GLY.

Note: *Randomization ratio (switched:continued baseline treatments) =3:1 by stratifying background medications.
Abbreviations: ICS, inhaled corticosteroid; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council; od, once daily.

Table 1 Definitions of clinically important deterioration

Definition	Combination of parameters
D1	Decrease of ≥100 mL in trough FEV1 from baseline or decrease of ≥1 point in TDI or incidence of AECOPD during the study
D2	Decrease of ≥100 mL in trough FEV1 from baseline or increase in ≥0.4 point in CCQ from baseline or incidence of AECOPD during the study
D3	Decrease of ≥100 mL in trough FEV1 from baseline or decrease of ≥1 point in TDI or increase in ≥0.4 point in CCQ from baseline or incidence of AECOPD during the study

Note: An AECOPD was defined as worsening of COPD which was managed with short-acting bronchodilators and a systemic corticosteroid or antibiotic, or a combination of both.

Abbreviations: AECOPD, acute exacerbation of moderate/severe COPD; CCQ, clinical COPD questionnaire; FEV₁, forced expiratory volume in 1 second; TDI, transition dyspnea index.

Table 2 Demographics and baseline characteristics of patients (ITT population)

Characteristic	mMRC score ≥1		mMRC score ≥2
	LABA + ICS (n=269)	IND/GLY (n=811)	LABA or LAMA (n=268)	IND/GLY (n=811)
Age, years	64.4±8.9	64.6±8.7	65.2±7.6	65.4±8.3
Male, n (%)	164 (61.0)	528 (65.1)	176 (65.7)	537 (66.2)
Current smoker, n (%)	138 (51.3)	392 (48.3)	135 (50.4)	435 (53.6)
Post-bronchodilator FEV1, L	1.8±0.5	1.8±0.5	1.8±0.4	1.8±0.5
Post-bronchodilator FEV1, % predicted	63.3±8.3	63.7±8.7	63.5±8.2	63.8±8.8
Dyspnea – mMRC grade, n (%)
1	138 (51.3)	435 (53.6)	28 (10.4)	63 (7.8)
≥2	129 (48.0)	365 (45.0)	238 (88.8)	745 (91.9)
Number of patients with exacerbations in the previous 12 months, n (%)
1	72 (26.8)	220 (27.1)	56 (20.9)	136 (16.8)
≥2	4 (1.5)	4 (0.5)	0 (0.0)	4 (0.5)
CCQ total score	2.0±1.0	2.0±1.0	2.2±0.9	2.2±0.9

Note: Data are presented as mean ± SD, unless otherwise stated.

Abbreviations: CCQ, clinical COPD questionnaire; FEV₁, forced expiratory volume in 1 second; IND/GLY, indacaterol/glycopyrronium; ITT, intention-to-treat; LABA + ICS, long-acting β₂-agonist + inhaled corticosteroid; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council.

Table 3 Effect of IND/GLY on individual outcome measures compared with LABA or LAMA

Outcome measures	IND/GLYa (n=811)	LABA or LAMAa (n=268)	IND/GLY versus LABA or LAMA odds ratio (95% CI)
Decrease in trough FEV1 of ≥100 mL	100 (12.3)	74 (27.6)	0.37 (0.26–0.52)
Decrease in TDI of ≥1 point	72 (8.9)	42 (15.7)	0.55 (0.37–0.83)
Increase in CCQ of ≥0.4 point	93 (11.5)	51 (19.0)	0.55 (0.38–0.81)
Incidence of AECOPDb	44 (5.4)	19 (7.0)	0.75 (0.43–1.31)

Notes:

a Patients had mMRC ≥2.

b As adverse event reporting. Data presented as number and percentage of patients with clinically important deterioration, unless otherwise specified.

Abbreviations: AECOPD, acute exacerbation of moderate/severe COPD; CCQ, clinical COPD questionnaire; FEV₁, forced expiratory volume in 1 second; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council; TDI, transition dyspnea index.

Figure 2 Effect of IND/GLY on CID compared with LABA or LAMA for each CID definition.

Notes: *Patients had mMRC ≥2. Definitions of D1, D2, and D3 are described in Table 1.
Abbreviations: CID, clinically important deterioration; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council.

Table 4 Effect of IND/GLY on individual outcome measures compared with LABA + ICS

Outcome measures	IND/GLY (n=811)	LABA + ICS (n=269)	IND/GLY versus LABA + ICS odds ratio (95% CI)
Decrease in trough FEV1 of ≥100 mL	126 (15.5)	61 (22.7)	0.66 (0.47–0.93)
Decrease in TDI of ≥1 point	91 (11.2)	39 (14.5)	0.81 (0.54–1.21)
Increase in CCQ of ≥0.4 point	113 (13.9)	48 (17.8)	0.79 (0.54–1.15)
Incidence of AECOPDa	63 (7.8)	16 (5.9)	1.33 (0.76–2.35)

Notes:

a As adverse event reporting. Data presented as number and percentage of patients with clinically important deterioration, unless otherwise specified.

Abbreviations: AECOPD, acute exacerbation of moderate/severe COPD; CCQ, clinical COPD questionnaire; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β₂-agonist; TDI, transition dyspnea index.

Figure 3 Effect of IND/GLY on CID compared with LABA + ICS for each CID definition.

Notes: Data are presented as odds ratio (95% CI). Definitions of D1, D2, and D3 are described in Table 1.
Abbreviations: CID, Clinically important deterioration; ICS, inhaled corticosteroid; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β₂-agonist.